Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in Mice

Abstract

This study sought to determine whether invariant NKT (iNKT) cells play an essential role in inflammation-induced preterm delivery. Preterm delivery and fetal death rates were determined in wild-type (WT) C57BL/6 mice and iNKT cell-deficient Jα18−/− mice injected i.p. with LPS. The percentages of decidual immune cells, including activated subsets, and costimulatory molecule expression were analyzed by flow cytometry. Th1 and Th2 cytokine production in the culture supernatants of decidual mononuclear cells was measured by ELISA. To some extent, Jα18−/− mice were resistant to LPS-induced preterm delivery. The proportions of decidual CD3+ and CD49b+ cells were slightly lower in Jα18−/− mice than in WT Jα18+/+ mice, whereas almost no CD3+CD49b+ cells could be found in Jα18-null mice. The percentages of activated decidual DCs, T cells, and NK cells were significantly lower in LPS-treated Jα18−/− mice than in WT mice. The CD40, CD80, and CD86 expression levels on decidual CD11c+ cells from Jα18−/− mice were also significantly lower than in WT mice. Mean concentrations of Th1 cytokines IFN-γ and IL-12p70 in the culture supernatants of decidual mononuclear cells from LPS-treated Jα18−/− mice were apparently lower than those of LPS-induced WT mice. Additionally, the proportions of activated CD11c+ cells, CD3+ cells, and CD49b+ cells in LPS-induced preterm delivery mice were strikingly higher in both WT and null mice when compared with the control PBS group and LPS-injected but normally delivered mice. Our results suggest that iNKT cells may play an essential role in inflammation-induced preterm birth.

Immune cells in term and preterm labor

“…136 The injection of LPS at 15 dpc caused preterm birth in wild-type mice but not in iNKT cell-deficient mice, 136 suggesting that iNKT cells modulate the process of labor induced by microbial products. Conversely, the stimulation of iNKT cells in vivo by injection of α-galactosylceramide during late gestation (16 dpc) induced early preterm birth (17 dpc), 128 which may be due to an expansion of NK1.1 + TCRαβ + NKT cells in the uterus.…”

Anakinra and etanercept prevent embryo loss in pregnant nonobese diabetic mice

“…For comparison of multiple variables, ANOVA was used. Differences were considered to be statistically significant when P!0.05 (Ilievski & Hirsch 2010, Li et al 2012.…”

“…Many studies have attempted to study the etiopathogenesis of pregnancy failure, and microbial infection has emerged as an important cause of pregnancy failure in many of these studies. A large body of evidence indicates that inflammatory cytokines and chemokines are involved in bacterial and viral infections (Lin et al 2009a, Ilievski & Hirsch 2010, Li et al 2012. Further data highlighting the significant relationship between Toll-like receptors (TLRs) and adverse pregnancy outcomes have drawn considerable attention (Filipovich et al 2009, Lin et al 2009b,c, 2014, Sun et al 2013.…”

Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface

“…Several techniques have been described that facilitate the isolation of infiltrating leukocytes from the murine tissues at the maternal-fetal interface throughout pregnancy 31,38,39,[43][44][45][46] . The protocol described herein offers a novel approach that combines the use of gentle mechanical and enzymatic tissue dissociation techniques to preserve the integrity of extracellular markers in the leukocytes isolated from the placenta and the decidual and uterine tissues of mice.…”

“…Several studies have reported the use of trypsin 32 , collagenase 37 , DNase 31 , dispase 38 , and commercial cocktails of various enzymes 32,39 . However, the nature and concentration of different enzymes and the duration of digestion must be meticulously defined and validated in order to ensure maintenance of the integrity of the cell surface antigenic epitopes required for immunophenotyping.…”